Robotic living donor hepatectomy is associated with superior outcomes for both the donor and the recipient compared with laparoscopic or open - A single-center prospective registry study of 3448 cases.

Minimally invasive donor hepatectomy is an emerging surgical technique in living donor liver transplantation (LDLT). We examined outcomes across open, laparoscopic, and robotic LDLT using a prospective registry. We analyzed 3448 cases (1724 donor-recipient pairs) from January 2011 to March 2023 (NCT06062706). Among donors, 520 (30%) were female. Adult-to-adult LDLT comprised 1061 (62%) cases. A total of 646 (37%) of the donors underwent open, 165 (10%) laparoscopic, and 913 (53%) robotic hepatectomies. Primary outcomes: donor overall morbidity was 4% (35/903) for robotic, 8% (13/165) laparoscopic, and 16% (106/646) open (P < .001) procedures. Pediatric and adult recipient mortality was similar among the 3 donor hepatectomy approaches: robotic 1.5% and 7.0%, compared with 2.3% and 8.3% laparoscopic, and 1.6% and 5.5% for open donor surgery, respectively (P = .802, P = .564). Secondary outcomes: pediatric and adult recipients major morbidity after robotic hepatectomy was 15% and 23%, compared with 25% and 44% for laparoscopic surgery and 19% and 31% for open surgery, respectively (P = .033, P < .001). Graft and recipient 5-year survival were 90% and 93% for pediatrics and 79% and 80% for adults, respectively. In conclusion, robotic LDLT was associated with superior outcomes when compared with the laparoscopic and open approaches. Both donors and, for the first time reported, recipients benefitted from lower morbidity rates in robotic surgery, emphasizing its potential for further advancing this field.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Revolutionizing Organ Transplantation with Robotic Surgery.

OBJECTIVE: To evaluate the impact of robotic techniques on organ transplantation outcomes. SUMMARY BACKGROUND DATA: The evolution of organ transplantation is becoming influenced by the adoption of minimally invasive techniques, transitioning from laparoscopic to robotic methods. Robotic surgery has emerged as a significant advancement, providing superior precision and outcomes compared to traditional approaches. METHODS: This perspective includes a systematic review of the literature, original data from a high-volume center, as well as an international survey focusing on perceptions related to robotic versus laparoscopic and open approaches. RESULTS: The systematic review and meta-analysis revealed lower morbidity with robotic donor nephrectomy, recipient kidney transplant and donor hepatectomy. Our center's experience, with over 3,000 minimally invasive transplant procedures (kidney, liver, donor, and recipient), supports the superiority of Robotic Transplant Surgery (RTS). The global survey confirms this shift, revealing a preference for robotic approaches due to their reduced morbidity, despite challenges such as access to the robotic system and cost. CONCLUSION: This comprehensive overview including a systematic review, original data, and perceptions derived from the international survey demonstrate the superiority of Robotic Transplant Surgery (RTS) across a range of organ transplantations, for both donors and recipients. The future of RTS depends on the efforts of the surgical community in addressing challenges such as economic implications, the need for specialized surgical training for numerous surgeons, as well as wide access to robotic systems worldwide.

Decoding the Clavien-Dindo Classification: Artificial Intelligence (AI) as a Novel Tool to Grade Postoperative Complications.

OBJECTIVE: To assess ChatGPT's capability of grading postoperative complications using the Clavien-Dindo classification (CDC) via Artificial Intelligence (AI) with Natural Language Processing (NLP). BACKGROUND: The CDC standardizes grading of postoperative complications. However, consistent, and precise application in dynamic clinical settings is challenging. AI offers a potential solution for efficient automated grading. METHODS: ChatGPT's accuracy in defining the CDC, generating clinical examples, grading complications from existing scenarios, and interpreting complications from fictional clinical summaries, was tested. RESULTS: ChatGPT 4 precisely mirrored the CDC, outperforming version 3.5. In generating clinical examples, ChatGPT 4 showcased 99% agreement with minor errors in urinary catheterization. For single complications, it achieved 97% accuracy. ChatGPT was able to accurately extract, grade, and analyze complications from free text fictional discharge summaries. It demonstrated near perfect performance when confronted with real-world discharge summaries: comparison between the human and ChatGPT4 grading showed a κ value of 0.92 (95% CI 0.82-1) (P<0.001). CONCLUSIONS: ChatGPT 4 demonstrates promising proficiency and accuracy in applying the CDC. In the future, AI has the potential to become the mainstay tool to accurately capture, extract, and analyze CDC data from clinical datasets.

Outcomes of Adult Right Graft Living Donor Liver Transplantation Utilizing the Robotic Platform Integrated Real-time Indocyanine Green Fluorescence Cholangiography Compared to the Open Approach.

OBJECTIVE: This study aimed to assess short-term biliary outcomes in adult living donor liver transplants using right grafts, comparing robotic surgery with real-time indocyanine green fluorescence cholangiography (ICG-CA) for optimal hilar plate transection, against the conventional open approach. SUMMARY BACKGROUND DATA: Determining the optimal transection plane through the hilar plate is crucial in donor hepatectomies, impacting outcomes significantly. PATIENTS AND METHODS: From 2011 to 2023, a total of 839 right graft living donor hepatectomies were performed, with 414 (49%) performed via the open approach and 425 (51%) utilizing the robotic platform. RESULTS: The MRCP predictions correlated moderately with the actual count of graft ducts (r=0.57,P<0.001) Out of all 839 right donor hepatectomies, 321 (44%) were single duct grafts, of which 193/425 (49%) were retrieved with the robotic while 128/414 (38%) were with the open approach (OR 1.58, 95% CI 1.16-2.14),P=0.003). Overall, 50 (6%) of the donors developed a biliary complication during hospital stay, of whom 38 (9%) were grafts retrieved with the open, while 13 (3%) with the robotic approach (OR 0.31, 95% CI 0.15-0.61,P<0.001). Similarly, 63 (15%) of the adult recipients developed a biliary complication of any severity when grafts were retrieved with the open approach compared to 35 (8%) with the robotic approach (OR 0.50, 95% CI 0.31-0.79),P=0.002). CONCLUSION: The robotic platform with integrated real-time ICG-CA during right donor hepatectomy offers improved safety for the donor by accurately addressing the right hilar corridor, resulting in fewer graft ducts, and fewer complications of the donor and recipient when compared to the standard open approach.

Comparative outcomes of Living Donor Liver Transplantation in elderly recipients: A study on morbidity and survival in 1,018 recipients.

BACKGROUND AND AIMS: Given the increasing demand of patients requiring liver transplant who are 70 years or older and have may have health conditions, this study aimed to assess the outcomes of Living Donor Liver Transplant (LDLT) recipients, in this age group. METHODS: We conducted an analysis using a prospective registry that included all LDLT recipients from January 2011 to May 2023. Patients into two age groups; 18-69 years and 70 years or older and compared their short- term and long-term outcomes. We considered complications as major if they were Grade ≥3a (Dindo-Clavian). RESULTS: Among 1018 LDLT recipients, 71 (7%) were aged 70 years or older. The rates of post-transplant complications of any severity were comparable between the younger and older age groups (467% vs. 46%, p =0.983), as were the rates of major complications (25% vs. 25%, p =0.995) and in-hospital mortality (6% vs. 7%, p =0.800). The 1-, 3-, and 5-year graft survival rates were 94%, 86%, and 81% in the younger group and 92%, 87%, and 65% in the older group ( p =0.090). Similarly, the overall 1-, 3-, and 5-year recipient survival rates were 90%, 85%, and 86% in the younger group and 88%, 86%, and 65% in the older group ( p =0.100). CONCLUSION: This study suggests that carefully selected elderly patients can undergo LDLT and achieve comparable short-term outcomes to their younger counterparts.

Insight into prevalence, etiology, and modalities of pediatric chronic dialysis: a comprehensive nationwide analysis.

BACKGROUND: This study aimed to determine the prevalence and etiology of kidney failure (KF) among children below 15 years of age receiving chronic dialysis in Saudi Arabia and describe their dialysis modalities. METHODS: This cross-sectional descriptive study was conducted on 8 August 2022, encompassing all 23 pediatric dialysis centers in Saudi Arabia. Data gathered comprised patient demographics, causes of KF, and the dialysis methods employed. Collected data underwent analysis to determine prevalence of children undergoing chronic dialysis, discern underlying causes of KF, and evaluate distribution of patients across different dialysis modalities. RESULTS: The prevalence of children on chronic dialysis is 77.6 per million children living in Saudi Arabia, equating to 419 children. The predominant underlying cause of KF was congenital anomalies of the kidneys and urinary tract (CAKUT), representing a substantial 41% of cases. Following this, others or unknown etiologies accounted for a noteworthy 25% of cases, with focal segmental glomerulosclerosis (FSGS) comprising 13%, glomerulonephritis at 11%, and congenital nephrotic syndrome contributing 10% to etiological distribution. Regarding dialysis modalities employed, 67% of patients were on peritoneal dialysis (PD), while the remaining 33% were on hemodialysis (HD). CONCLUSIONS: This first nationwide study of pediatric chronic dialysis in Saudi Arabia sheds light on the prevalence of children undergoing chronic dialysis and underlying causes of their KF, thereby contributing to our understanding of clinical management considerations. This research serves as a stepping stone for the development of national registries.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Machine learning improves the accuracy of graft weight prediction in living donor liver transplantation.

Precise graft weight (GW) estimation is essential for planning living donor liver transplantation to select grafts of adequate size for the recipient. This study aimed to investigate whether a machine-learning model can improve the accuracy of GW estimation. Data from 872 consecutive living donors of a left lateral sector, left lobe, or right lobe to adults or children for living-related liver transplantation were collected from January 2011 to December 2019. Supervised machine-learning models were trained (80% of observations) to predict GW using the following information: donor's age, sex, height, weight, and body mass index; graft type (left, right, or left lateral lobe); computed tomography estimated graft volume and total liver volume. Model performance was measured in a random independent set (20% of observations) and in an external validation cohort using the mean absolute error (MAE) and the mean absolute percentage error and compared with methods currently available for GW estimation. The best-performing machine-learning model showed an MAE value of 50 ± 62 g in predicting GW, with a mean error of 10.3%. These errors were significantly lower than those observed with alternative methods. In addition, 62% of predictions had errors <10%, whereas errors >15% were observed in only 18.4% of the cases compared with the 34.6% of the predictions obtained with the best alternative method ( p < 0.001). The machine-learning model is made available as a web application ( http://graftweight.shinyapps.io/prediction ). Machine learning can improve the precision of GW estimation compared with currently available methods by reducing the frequency of significant errors. The coupling of anthropometric variables to the preoperatively estimated graft volume seems necessary to improve the accuracy of GW estimation.

Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference.

The practice of LDLT currently delivers limited impact in western transplant centers. The American Society of Transplantation organized a virtual consensus conference in October 2021 to identify barriers and gaps to LDLT growth, and to provide evidence-based recommendations to foster safe expansion of LDLT in the United States. This article reports the findings and recommendations regarding innovations and advances in approaches to donor-recipient matching challenges, the technical aspects of the donor and recipient operations, and surgical training. Among these themes, the barriers deemed most influential/detrimental to LDLT expansion in the United States included: (1) prohibitive issues related to donor age, graft size, insufficient donor remnant, and ABO incompatibility; (2) lack of acknowledgment and awareness of the excellent outcomes and benefits of LDLT; (3) ambiguous messaging regarding LDLT to patients and hospital leadership; and (4) a limited number of proficient LDLT surgeons across the United States. Donor-recipient mismatching may be circumvented by way of liver paired exchange. The creation of a national registry to generate granular data on donor-recipient matching will guide the practice of liver paired exchange. The surgical challenges to LDLT are addressed herein and focuses on the development of robust training pathways resulting in proficiency in donor and recipient surgery. Utilizing strong mentorship/collaboration programs with novel training practices under the auspices of established training and certification bodies will add to the breadth and depth of training.

Coronavirus disease 2019 vaccine in pediatric post-kidney transplantation.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of persons worldwide. Many vaccines have been developed; however, their efficacy in pediatric solid organ transplant recipients is yet to be determined. METHODS: This is a prospective observational, non-interventional single-center study on the safety and efficacy of a COVID-19 vaccine (BNT162b2) in pediatric kidney transplant recipients. The primary aim of this study was to evaluate immunogenicity according to SARS-CoV-2-specific neutralizing antibody titer after two vaccine doses. The secondary aims were to investigate the safety of the vaccines, solicited local and systemic adverse reactions, incidence of COVID-19 post-vaccination, and effects on transplant graft function. Baseline investigations were conducted on pediatric renal transplant recipients, and recruited participants were advised to have the Comirnaty® mRNA vaccine according to protocol. RESULTS: A total of 48 patients (male, n = 31, 64.6%; female, n = 17, 35.4%), median age 14 [12-16] years were included, and all received two doses of the vaccine. The vaccine had a favorable safety and side-effect profile. The S-antibody titer of all patients ranged between .4 and 2,500 U/ml and was > 50 U/ml in 89% of the patients. No difference in the measured antibody immune response was noted between infected and uninfected children. No major side effects were reported. CONCLUSION: The vaccine had a favorable safety profile in 12- to 15-year-old kidney transplant recipients, producing a greater measured antibody response than that in older transplant recipients.

Robotic donor hepatectomy: A major breakthrough in living donor liver transplantation.

Living donation in many countries is the main resource of organs. Healthy, volunteering individuals deserve the highest safety standards possible in addition to the least invasive technique to procure the organs. Since the introduction of living donor liver transplantation, many efforts have been made to minimize the surgical trauma inherent to living donor surgery. The journey started with a large Mercedes incision and evolved to reverse L-shaped and small upper midline incisions before the introduction of minimally invasive laparoscopic techniques originated. The technical difficulties of the laparoscopic approach due to suboptimal instrumentation, challenging ergonomics, and the long learning curve limited the application of the fully laparoscopic approach to a few centers. The recent introduction of the robotic platform with its superb optical system and advanced instruments allows for the first time, a genuine emulation of open donor surgery in a closed abdomen, thus allowing all liver donors to benefit from minimally invasive surgery (better cosmesis, less pain and morbidity, and better quality of life) without compromising donor safety. This attribute in combination with the ubiquitous presence of the robot in major transplant centers may well lead to the desired endpoint of this technology, namely, the widespread dissemination of minimally invasive donor surgery.

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] µmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 µmol/L (P = 0.05) tended to be associated with improved NLS. CONCLUSIONS: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

CTLA4-Ig mediated immunosuppression favors immunotolerance and restores graft in mouse airway transplants.

CTLA4-Ig is a potent costimulatory blocker that inhibits T cell activation during alloimmune inflammation and increases graft survival and function. CTLA4-Ig-mediated immunosuppression has been demonstrated to support transplant function in various clinical trials and preclinical settings, but its effects on the balance between regulatory T cells (Tregs) and effector T cells (Teffs), as well as complement activation, are less well investigated. In the present study, we proposed to investigate the effects of CTLA4-Ig mediated immunosuppression on the phase of immunotolerance and the subsequent graft microvascular and epithelial repair during the progression of subepithelial fibrosis in a mouse model of orthotopic trachea transplantation. Briefly, CTLA4-Ig treated allografts (2 mg/kg, I.P.), untreated allografts, and syngrafts were serially monitored for peripheral FOXP3+ Tregs, antibody-mediated complement activation (C3d and C4d), tissue oxygenation, donor-recipient microvascular blood flow, and subsequent tissue remodeling following transplantation. Our data demonstrate that CTLA4-Ig mediated immunosuppression significantly results in late increases in both peripheral CD4+/CD8+ FOXP3+ Tregs and serum IL-10, but prevents the microvascular deposition of IgG, complement factor C3d, and epithelial C4d respectively, which proportionally improved blood flow and tissue oxygenation in the graft and, thus, promotes graft repair. Also, it restored the airway lumen, epithelium, and prevented the progression of subepithelial collagen deposition up to 90 days after transplantation. This study demonstrates that CTLA4-Ig-mediated immunosuppression potentially modulates both effector response and a late surge of regulatory activity to preserve graft microvasculature and rescue allograft from sustained hypoxia and ischemia and thereby limits subepithelial fibrosis.

Influence of surgical technique in donor hepatectomy on immediate and short-term living donor outcomes - A systematic review of the literature, meta-analysis, and expert panel recommendations.

BACKGROUND: There are currently no guidelines pertaining to ERAS pathways in living donor hepatectomy. OBJECTIVES: The aim of this study was to identify whether surgical technique influences immediate and short-term outcomes after living liver donation surgery. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review and meta-analysis following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel (CRD42021260707). Endpoints were mortality, overall complications, serious complications, bile eaks, pulmonary complications, estimated blood loss and length of stay. RESULTS: Of the 2410 screened articles, 21 articles were included for final analysis; three observational, 13 retrospective cohort, four prospective cohort studies, and one randomized trial. Overall complications were higher with right versus left hepatectomy (26.8% vs. 20.8%; OR 1.4, P = .010). Donors after left hepatectomy had shorter length of stay (MD 1.4 days) compared to right hepatectomy. There was no difference in outcomes after right donor hepatectomy with versus without middle hepatic vein. We had limited data on the influence of incision type and minimally invasive approaches on living donor outcomes, and no data on the effect of operative time on donor outcomes. CONCLUSIONS: Left donor hepatectomy should be preferred over right hepatectomy, as it is related to improved donor short-term outcomes (QOE; Moderate | Grade of Recommendation; Strong). Right donor hepatectomy with or without MHV has equivalent outcomes (QOE; Moderate | Grade of Recommendation; Strong); no preference is recommended, decision should be based on program's experience and expertise. No difference in outcomes was observed related to incision type, minimally invasive vs. open (QOE; Low | Grade of Recommendation; Weak); no preference can be recommended.

Comparison of the safety and immunogenicity of the BNT-162b2 vaccine and the ChAdOx1 vaccine for solid organ transplant recipients: a prospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials.

Robotic surgery and liver transplantation: A single-center experience of 501 robotic donor hepatectomies.

BACKGROUND: Over the past two decades robotic surgery has been introduced to many areas including liver surgery. Laparoscopic liver surgery is an alternative minimally invasive approach. However, moving on to the complexity of living donor hepatectomies, the advantages of robotic versus laparoscopic approach have convinced us to establish the robotic platform as a standard for living donor hepatectomy. METHODS: From November 2018 to January 2022, 501 fully robotic donor hepatectomies, including 177 left lateral donor lobes, 112 full left lobes and 212 full right lobes were performed. Grafts were donated to 296 adult recipients and 205 pediatric recipients. Donor age, sex, body weight, body mass index (BMI), graft weight, graft to body weight ratio (GBWR), operative time, blood loss, first warm ischemic time, pain score, length of intensive care unit (ICU) stay and hospital stay, and complications were retrospectively analyzed based on a prospectively kept database. Recipients were evaluated for graft and patient survival, age, sex, BMI, body weight, model of end-stage liver disease score, blood loss, transfusions, operative time, cold ischemic time, length of hospital stay and complications. RESULTS: There was no donor mortality. Two cases needed to be converted to open surgery. The median blood loss was 60 mL (range 20-800), median donor operative time was 6.77 h (range 2.93-11.53), median length of hospital stay was 4 days (range 2-22). Complication rate in donors classified following Clavien-Dindo was 6.4% (n = 32) with one grade III complication. Three-year actual recipient overall survival was 91.4%; 87.5% for adult recipients and 97.1% for pediatric recipients. Three-year actual graft overall survival was 90.6%; 87.5% for adult recipients and 95.1% for pediatric recipients. In-hospital mortality was 6%, 9.1% (27/296) for adult recipients and 1.4% (3/205) for pediatric recipients. The recipients' morbidity was 19.8% (n = 99). Twenty-eight recipients (5.6%) had biliary and 22 (4.4%) vascular complications. Six (12.0%) recipients needed to be re-transplanted. CONCLUSIONS: With growing experience it is nowadays possible to perform any donor hepatectomy by robotic approach regardless of anatomical variations and graft size. Donor morbidity and quality for life results are encouraging and should motivate other transplant centers with interest in minimally invasive donor surgery to adopt this robotic technique.

Targeting Interleukin-10 Restores Graft Microvascular Supply and Airway Epithelium in Rejecting Allografts.

Interleukin-10 (IL-10) is a vital regulatory cytokine, which plays a constructive role in maintaining immune tolerance during an alloimmune inflammation. Our previous study highlighted that IL-10 mediated immunosuppression established the immune tolerance phase and thereby modulated both microvascular and epithelial integrity, which affected inflammation-associated graft malfunctioning and sub-epithelial fibrosis in rejecting allografts. Here, we further investigated the reparative effects of IL-10 on microvasculature and epithelium in a mouse model of airway transplantation. To investigate the IL-10 mediated microvascular and epithelial repair, we depleted and reconstituted IL-10, and monitored graft microvasculature, airway epithelium, and associated repair proteins. Our data demonstrated that both untreated control allografts and IL-10 (-) allografts showed a significant early (d6) increase in microvascular leakiness, drop-in tissue oxygenation, blood perfusion, and denuded airway epithelium, which is associated with loss of adhesion protein Fascin-1 and ß-catenin on vascular endothelial cells at d10 post-transplantation. However, IL-10 (+) promotes early microvascular and airway epithelial repair, and a proportional increase in endothelial Fascin-1, and ß-catenin at d10 post-transplantation. Moreover, airway epithelial cells also express a significantly higher expression of FOXJ1 and ß-catenin in syngrafts and IL-10 (+) allografts as compared to IL-10 (-) and untreated controls at d10 post-transplantation. Collectively, these findings demonstrated that IL-10 mediated microvascular and epithelial changes are associated with the expression of FOXJ1, ß-catenin, and Fascin-1 proteins on the airway epithelial and vascular endothelial cells, respectively. These findings establish a potential reparative modulation of IL-10 associated microvascular and epithelial repair, which could provide a vital therapeutic strategy to facilitate graft repair in clinical settings.

Expert Consensus Guidelines on Minimally Invasive Donor Hepatectomy for Living Donor Liver Transplantation From Innovation to Implementation: A Joint Initiative From the International Laparoscopic Liver Society (ILLS) and the Asian-Pacific Hepato-Pancreato-Biliary Association (A-PHPBA).

OBJECTIVE: The Expert Consensus Guidelines initiative on MIDH for LDLT was organized with the goal of safe implementation and development of these complex techniques with donor safety as the main priority. BACKGROUND: Following the development of minimally invasive liver surgery, techniques of MIDH were developed with the aim of reducing the short- and long-term consequences of the procedure on liver donors. These techniques, although increasingly performed, lack clinical guidelines. METHODS: A group of 12 international MIDH experts, 1 research coordinator, and 8 junior faculty was assembled. Comprehensive literature search was made and studies classified using the SIGN method. Based on literature review and experts opinions, tentative recommendations were made by experts subgroups and submitted to the whole experts group using on-line Delphi Rounds with the goal of obtaining >90% Consensus. Pre-conference meeting formulated final recommendations that were presented during the plenary conference held in Seoul on September 7, 2019 in front of a Validation Committee composed of LDLT experts not practicing MIDH and an international audience. RESULTS: Eighteen Clinical Questions were addressed resulting in 44 recommendations. All recommendations reached at least a 90% consensus among experts and were afterward endorsed by the validation committee. CONCLUSIONS: The Expert Consensus on MIDH has produced a set of clinical guidelines based on available evidence and clinical expertise. These guidelines are presented for a safe implementation and development of MIDH in LDLT Centers with the goal of optimizing donor safety, donor care, and recipient outcomes.